New tuberculosis vaccines

Martín Montañés, Carlos; Gicquel, Brigitte

doi:10.1016/S0213-005X(11)70019-2

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Abstract

The current tuberculosis (TB) vaccine, bacille Calmette-Guerin (BCG), is a live vaccine used worldwide, as it protects against severe forms of the disease, saving thousands of lives every year, but its efficacy against pulmonary forms of TB, responsible for transmission of the diseases, is variable.

For more than 80 years now no new TB vaccines have been successfully developed. Over the last decade the effort of the scientific community has resulted in the design and construction of promising vaccine candidates. The goal is to develop a new generation of vaccines effective against respiratory forms of the disease. We will focus this review on new prophylactic vaccine candidates that aim to prevent TB diseases.

Two are the main strategies used to improve the immunity conferred by the current BCG vaccine, by boosting it with new subunit vaccines, and a second strategy is focused on the construction of new more effective live vaccines, capable to replace the current BCG and to be used as prime vaccines.

After rigorous preclinical studies in different animal models new TB vaccine candidates enter in clinical trials in humans. First, a small Phase I for safety followed by immunological evaluation in Phase II trials and finally evaluated in large population Phase III efficacy trials in endemic countries. At present BCG prime and boost with different subunit vaccine candidates are the more advanced assessed in Phase II. Two prime vaccines (based on recombinant BCG) have been successfully evaluated for safety in Phase I trials. A short number of live attenuated vaccines are in advance preclinical studies and the candidates ready to enter Phase I safety trials are produced under current good manufacturing practices.

Keywords:

Bacille Calmette-Guerin (BCG)

Tuberculosis

Subunit vaccines

Live vaccines

Resumen

La actual vacuna contra la tuberculosis, bacilo de Calmette-Guerin (BCG), en uso desde 1921, protege contra las formas más graves de la enfermedad, pero su eficacia es muy variable contra las formas de tuberculosis pulmonar, por lo que la investigación y desarrollo de nuevas vacunas es un reto importante para la comunidad científica.

En la última década, importantes esfuerzos en investigación han dado como resultado el diseño y construcción de nuevos candidatos a vacunas contra la tuberculosis. El objetivo es desarrollar una nueva generación de vacunas eficaces contra las formas respiratorias de la enfermedad, responsables de la transmisión de la tuberculosis.

Esta revisión se centra en el progreso preclínico y clínico de nuevas vacunas profilácticas, dirigidas a prevenir la enfermedad. Dos son las principales estrategias: la primera busca mejorar la inmunidad conferida por BCG, revacunando con vacunas subunidades, y la segunda estrategia se centra en la construcción de nuevas vacunas vivas más eficaces, capaces de sustituir la actual BCG.

Tras rigurosos estudios preclínicos en modelos animales, algunos candidatos a la vacuna contra la tuberculosis han entrado en ensayos clínicos en humanos. Actualmente, las vacunas subunidades son las más avanzadas en estos ensayos y están siendo evaluadas en fase II en individuos previamente vacunados con BCG. Vacunas vivas basadas en BCG recombinante se están evaluado en fase I, y nuevas vacunas vivas atenuadas han mostrado buenos resultados de atenuación y protección en estudios preclínicos, y están listas para entrar en ensayos de fase I en humanos.

Palabras clave:

Bacilo de Calmette-Guérin (BCG)

Tuberculosis

Vacunas subunidades

Vacunas vivas atenuadas

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